Deglycosylated human chorionic gonadotropin (DhCG) bound with high affinity to murine Leydig tumor cells but did not stimulate adenylate cyclase. DhCG blocked the binding and action of native hCG and therefore behaved as an antagonist. Whereas as exposure of the cells to hCG caused desensitization of hCG-stimulated adenylate cyclase and down-regulation of hCG-receptors, DhCG did not. Thus, receptor occupancy is not sufficient for these processes to occur. When cells containing bound DhCG were exposed to antibodies to hCG, adenylate cyclase was stimulated. No effect was observed by the antibodies alone or when added before DhCG. Fab, but not Fc, fragments of the antibodies also were effective. Thus, DhCG is converted from an antogonist to an agonist when certain antibodies bind to it. The most likely possibility is that the antibodies induce a change in conformation of the hormone that is crucial for its agonistic properties. Exposure of murine Leydig tumor cells to tumor promoting phorbol esters caused desensitization of hCG-stimulated adenylate cyclase. The number and affinity of hCG-receptors remained unchanged. Inactive phorbol esters had no effect. The cells contained a large number of high affinity sites for phorbol esters. Others have implicated the phorbol ester receptor as the calcium-activated, phospholipid-dependent protein kinase C. This was tested by treating the cells with the endogenous activator of protein kinase C, diacylglycerol, which also caused desensitization. Finally, phorbol esters stimulated the phosphorylation of many cellular proteins. As desensitization mediated by phorbol esters was analogous to that mediated by hCG, phosphorylation by protein kinase C may be involved in the mechanism of hormone-induced desensitization. This possibility was supported by the observation that phorbol esters also caused desensitization of catecholamine-stimulated adenylated cyclase in rat glioma C6 cells.